STUDY DESIGN: This study investigated the morphology, pathogenesis, and inheritance of idiopathic-like spinal curvature in the guppy syndrome, curveback. OBJECTIVE: To determine whether curveback could be applied as a model for the primary factors that contribute to heritable spinal curvature in humans, specifically, the etiopathogenesis of human familial idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: Although a genetic basis is accepted, phenotypic complexity and the lack of an animal model with noninduced curvature have made identification of idiopathic scoliosis etiology difficult. It is well established that humans and fish share many genes with similar tissue and temporal expression characteristics, and comparisons between human and fish genomes have proven to be valuable for understanding the genetics of diseases affecting humans. METHODS: The curveback lineage of guppies was constructed from a single curved male crossed to a normal female. Offspring (103) from the original cross were scored from birth until death for the presence and magnitude of spinal curvature. Genetic architecture was investigated through selective inbreeding, analysis of the distribution of curve magnitude in the mature population, and assessment of curve dynamics during development. Computed tomography assessed vertebral detail. RESULTS: Computed tomography reveals that vertebral breakage or fusion is not associated with the curveback syndrome. Inbreeding demonstrates a strong genetic influence on curveback, and the distribution of curve magnitude among adult fish suggests polygenic inheritance. There is a female bias for curves of high magnitude and curves that resolve before maturity. There is developmental variability for the age of curve onset, curve progression, and final curve magnitude. CONCLUSIONS: Observed parallels between the curveback syndrome and human idiopathic scoliosis suggest that the guppy model is an unexploited resource for the identification of primary etiological factors involved in curvature. As models for biomedical research, teleosts offer great potential regarding spinal stability and deformity.
STUDY DESIGN: This study investigated the morphology, pathogenesis, and inheritance of idiopathic-like spinal curvature in the guppy syndrome, curveback. OBJECTIVE: To determine whether curveback could be applied as a model for the primary factors that contribute to heritable spinal curvature in humans, specifically, the etiopathogenesis of humanfamilial idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: Although a genetic basis is accepted, phenotypic complexity and the lack of an animal model with noninduced curvature have made identification of idiopathic scoliosis etiology difficult. It is well established that humans and fish share many genes with similar tissue and temporal expression characteristics, and comparisons between human and fish genomes have proven to be valuable for understanding the genetics of diseases affecting humans. METHODS: The curveback lineage of guppies was constructed from a single curved male crossed to a normal female. Offspring (103) from the original cross were scored from birth until death for the presence and magnitude of spinal curvature. Genetic architecture was investigated through selective inbreeding, analysis of the distribution of curve magnitude in the mature population, and assessment of curve dynamics during development. Computed tomography assessed vertebral detail. RESULTS: Computed tomography reveals that vertebral breakage or fusion is not associated with the curveback syndrome. Inbreeding demonstrates a strong genetic influence on curveback, and the distribution of curve magnitude among adult fish suggests polygenic inheritance. There is a female bias for curves of high magnitude and curves that resolve before maturity. There is developmental variability for the age of curve onset, curve progression, and final curve magnitude. CONCLUSIONS: Observed parallels between the curveback syndrome and humanidiopathic scoliosis suggest that the guppy model is an unexploited resource for the identification of primary etiological factors involved in curvature. As models for biomedical research, teleosts offer great potential regarding spinal stability and deformity.
Authors: Kristen F Gorman; Julian K Christians; Jennifer Parent; Roozbeh Ahmadi; Detlef Weigel; Christine Dreyer; Felix Breden Journal: BMC Genet Date: 2011-01-26 Impact factor: 2.797
Authors: Jillian G Buchan; Ryan S Gray; John M Gansner; David M Alvarado; Lydia Burgert; Jonathan D Gitlin; Christina A Gurnett; Matthew I Goldsmith Journal: Dev Dyn Date: 2014-10-20 Impact factor: 3.780
Authors: Swarkar Sharma; Douglas Londono; Walter L Eckalbar; Xiaochong Gao; Dongping Zhang; Kristen Mauldin; Ikuyo Kou; Atsushi Takahashi; Morio Matsumoto; Nobuhiro Kamiya; Karl K Murphy; Reuel Cornelia; John A Herring; Dennis Burns; Nadav Ahituv; Shiro Ikegawa; Derek Gordon; Carol A Wise Journal: Nat Commun Date: 2015-03-18 Impact factor: 14.919